6′,6-bis-(1-phosphanorbornadiene) diphosphines

ABSTRACT

A subject of the present invention is new 6,6′-bis-(1-phosphanorbornadiene) diphosphines, their preparation process and their use in asymmetrical catalysis. 
     The new diphosphines correspond to general formula (I):

This is the national phase of PCT/FR98/00424, filed Mar. 4, 1998, nowWO98/39345.

A subject of the present invention is new6,6′-bis-(1-phosphanorbornadiene) diphosphines and their preparationprocess.

Another subject of the invention is said optically active disphosphines.

Finally, other subjects are the uses of these diphosphines, inparticular in asymmetrical synthesis in organic chemistry.

In numerous fields, in particular pharmaceutical, agro-chemical orperfumery fields, a growing demand has been noted for optically activeproducts which must have a useful property.

During synthesis of such products, the simultaneous production of aninactive enantiomer is generally observed which, by its presence, risksrendering a process uncompetitive from an industrial point of view.

Moreover, in certain fields (for example, pharmacology andagrochemistry), optically pure products are increasingly sought after,in order to avoid toxicity problems linked to the presence of theinactive enantiomer.

It is therefore important to minimize the formation of the enantiomer,which is not useful.

One of the means of achieving this is to conduct the reaction in thepresence of asymmetrical synthesis catalysts, which can be complexes oftransition metals with chiral ligands.

The problem which arises is that there are no universal chiral ligandswhich are suitable for conducting all chemical reactions and, given thedifficulty of obtaining the correct enantiomer with a high enantiomericexcess, it is important to have all sorts of chiral ligands available inorder to assess their performances.

Thus, in the Application PCT/FR95/01716, new optically active6,6′-bis-(1-phospha-2,3-diphenyl-4,5-dimethylnorbornadiene) diphosphineswere described, corresponding to the following formulae:

While this ligand allows useful hydrogenation catalysts to be obtainedfor hydrogenating certain a,b-unsaturated acids such asa-acetamidocinnamic acid, the enantiomeric excess obtained is notsatisfactory in all asymmetrical catalysis reactions.

It is therefore desirable to have other chiral ligands available whichcan be suitable if known ligands are insufficiently enantioselective.

The difficulty is that chiral ligands of diphosphine type are not easilyaccessible owing to their complex synthesis and also to the difficultyin separating diastereoisomers and/or enantiomers.

A first objective of the invention is to provide new diphosphines and aprocess for their preparation.

Another objective is to provide optically active diphosphines, chiral asregards phosphorus and non-racemizable.

Another objective is to provide modified diphosphines allowing betterresults to be obtained in asymmetrical catalysis reactions.

New products have now been found constituting the first subject of theinvention, namely 6,6′-bis-(1-phosphanorbornadiene) diphosphinescorresponding to the following formula:

in said formula (I):

R₁, R₂, R₃, R₄, R₅, identical or different, represent a hydrogen atom orhydrocarbon radical, optionally substituted, having from 1 to 40 carbonatoms, which can be a linear or branched, saturated or unsaturatedacyclic aliphatic radical; a monocyclic or polycyclic, saturated,unsaturated or aromatic, carbocyclic or heterocyclic radical; a linearor branched, saturated or unsaturated aliphatic radical, carrying acyclic substituent,

R₂ and R₃ together with the carbon atoms which carry them can form asaturated or unsaturated ring,

R₅ can represent a radical of

 type, in which R₁′, R₂′ and R₃′ have the same meaning as that given forR₁, R₂ and R₃,

R₄ , and R₅ cannot simultaneously represent a phenyl group.

In general formula (I), R₁, R₂, R₃, R₄, R₅, identical or different, canassume various meanings. Different examples are given hereafter but arein no way limitative.

Thus R₁ to R₅ can represent a linear or branched, saturated orunsaturated, acyclic aliphatic radical.

More precisely, R₁ to R₅ represent a linear or branched acyclicaliphatic radical preferably having 1 to 12 carbon atoms, saturated orcomprising one to several, generally 1 to 3, double bonds.

The hydrocarbon chain can optionally be interrupted by a group,preferably a heteroatom, and more particularly an oxygen or nitrogenatom or can carry substituents, for example a halogen atom, inparticular chlorine or a —CF₃ group.

It is also possible that in the diphosphine of formula (I), R₁ to R₅represent a linear or branched, saturated or unsaturated acyclicaliphatic radical which can optionally carry a cyclic substituent. Byring is understood a saturated, unsaturated or aromatic, carbocyclic orheterocyclic ring.

As examples of cyclic substituents, aromatic or heterocycliccycloaliphatic substituents can be envisaged, in particularcycloaliphatic substituents comprising 6 carbon atoms in the ring orbenzene substituents, these cyclic substituents themselves optionallycarrying one or more substituents.

As examples of such radicals there can be mentioned amongst others thebenzyl radical.

In general formula (I) for diphosphines, the R₁ to R₅ radicals can alsorepresent a carbocyclic radical, saturated or comprising 1 or 2unsaturations in the ring, generally having 3 to 8 carbon atoms,preferably 6 carbon atoms in the ring; said ring being able to besubstituted.

As preferred examples of R₁ to R₅ radicals, there can be mentioned thecyclohexyl radicals optionally substituted by linear or branched alkylradicals having 1 to 4 carbon atoms.

R₁ to R₅ can be saturated or unsaturated polycyclic carbocyclicradicals, preferably bicyclic, which means that at least two rings havetwo carbon atoms in common. In the case of the polycyclic compounds, thenumber of carbon atoms in each ring preferably varies from 3 to 6: thetotal number of carbon atoms preferably being equal to 7.

Thus, the R₁ to R₅ radicals preferentially represent an aromatichydrocarbon radical, and in particular a benzene radical correspondingto general formula (II):

in said formula (II):

n is an integer from 0 to 5, preferably from 0 to 3,

Q represents R₀, one of the following groups or functions:

a linear or branched alkyl radical having from 1 to 6 carbon atoms,preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,

a linear or branched alkenyl radical having from 2 to 6 carbon atoms,preferably from 2 to 4 carbon atoms, such as vinyl, allyl,

a linear or branched alkoxy radical having from 1 to 6 carbon atoms,preferably from 1 to 4 carbon atoms such as the methoxy, ethoxy,propoxy, isopropoxy, butoxy radicals,

an acyl group having from 2 to 6 carbon atoms,

a radical of formula:

—R₆—OH

—R₆—COOR₇

—R₆—CHO

—R₆—NO₂

—R₆—CN

—R₆—N(R₇)₂

—R₆—CO—N(R₇)₂

—R₆—SH

—R₆—X

—R₆—CF₃

—O—CF₃

in said formulae, R₆ represents a valency bond or a saturated orunsaturated, linear or branched, divalent hydrocarbon radical havingfrom 1 to 6 carbon atoms such as, for example, methylene, ethylene,propylene, isopropylene, isopropylidene; the R₇ radicals, identical ordifferent, represent a hydrogen atom or a linear or branched alkylradical having from 1 to 6 carbon atoms; X symbolizes a halogen atom,preferably a chlorine, bromine or fluorine atom.

Q represents R₀′, one of the following more complex radicals:

 in which:

m is an integer from 0 to 5, preferably from 0 to 3,

R₀ has the meaning indicated previously,

R₈ represents a valency bond; a saturated or unsaturated, linear orbranched divalent hydrocarbon group having from 1 to 6 carbon atoms suchas for example methylene, ethylene, propylene, isopropylene,isopropylidene or one of the following groups called Z:

—O—; —CO—; COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂—; —NR₇—CO—;

in said formulae, R₇ represents a hydrogen atom, a linear or branchedalkyl group having from 1 to 6 carbon atoms, preferably a methyl orethyl radical.

When n is greater than 1, the Q radicals can be identical or differentand 2 successive carbon atoms of the benzene ring can be joined togetherby a ketal bridge such as the extranuclear methylene dioxy or ethylenedioxy radicals.

Among all the aforementioned R₁ to R₅ radicals, the preferreddiphosphines correspond to general formula (I) in which R₁ to R₅represent an aromatic radical corresponding to general formula (II) inwhich:

n is equal to 0, 1, 2 or 3,

Q represents one of the following groups or functions:

a hydrogen atom

a linear or branched alkyl radical, having from 1 to 4 carbon atoms,

a linear or branched alkoxy radical having from 1 to 4 carbon atoms,

a benzoyl group,

an —OH group,

a —CHO group,

an NH₂ group,

an NO₂ group,

a phenyl radical,

a halogen atom,

a CF₃ group.

Even more preferentially, the compounds of formula (I) are chosen inwhich the identical or different Q radicals are a hydrogen atom, analkyl radical having from 1 to 4 carbon atoms.

As examples of radicals R₁ to R₅ corresponding to formula (I), there canbe mentioned more specifically the phenyl, tolyl or xylyl,1-methoxyphenyl, 2-nitrophenyl radicals, and the biphenyl,1,1′-methylenebiphenyl, 1,1′-isopropylidenebiphenyl,1,1′-carboxybiphenyl, 1,1′-oxybiphenyl, 1,1′-iminobiphenyl radicals:said radicals being able to be substituted by one or more substituents.

R₁ to R₅ can also represent a polycyclic aromatic hydrocarbon radical;the rings being able to form together ortho-condensed, ortho- andperi-condensed systems. There can more particularly be mentioned anaphthyl radical; said rings being able to be substituted.

In general formula (I) for diphosphines, R₁ to R₅ can also represent asaturated, unsaturated or aromatic heterocyclic radical, in particularcomprising 5 or 6 atoms in the ring including 1 or 2 heteroatoms such asthe nitrogen, sulphur and oxygen atoms; the carbon atoms of theheterocycle being optionally substituted.

R₁ to R₅ can also represent a polycyclic heterocyclic radical defined asbeing either a radical constituted by at least 2 aromatic heterocyclesor heterocycles not containing at least one heteroatom in each ring andforming together ortho- or ortho- and peri-condensed systems or aradical constituted by at least one aromatic or non-aromatic hydrocarbonring and at least one aromatic or non-aromatic heterocycle togetherforming ortho- or ortho- and peri-condensed systems; the carbon atoms ofsaid rings being optionally substituted.

As examples of R₁ to R₅ groups of heterocyclic type, there can bementioned among others the furyl, pyrrolyl, thienyl, isoxazolyl,furazannyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrannyl radicals and the quinolyl, naphthyridinyl,benzopyrannyl, benzofurannyl, indolyl radicals.

In the case where R₅ represents a radical of

type, R₁′ preferably represents a hydrogen atom and R₂′ and R₃′preferably represent a methyl radical.

It should be noted that if one of the R₁ to R₅ radicals comprises anyone ring, it is possible for this ring to carry a substituent.

The number of substituents present on the ring depends on the carboncondensation of the ring and the presence or absence of unsaturations onthe ring. The maximum number of substituents which can be carried by aring is easily determined by a person skilled in the art.

The substituent can be of any type provided that it does not interfereat the level of the desired product. R₀ illustrates the type ofsubstituents commonly encountered. The substituents carried most oftenby the ring are one or more alkyl or alkoxy radicals preferably having 1to 4 carbon atoms and/or a halogen atom.

In the case where the R₁ to R₅ radicals comprise an unsaturation such asa double bond, it is preferable for one of the carbon atoms of thedouble bond to be a disubstituted carbon, i.e. carrying two substituentsand there can in particular be mentioned the alkyl radicals preferablyhaving 1 to 4 carbon atoms.

As regards the R₂ and R₃ radicals, they can together with the carbonatoms which carry them form a saturated or unsaturated ring preferablyhaving from 5 to 7 carbon atoms and more preferentially 6 carbon atoms.It can be mentioned, among other things, that the R₂ and R₃ radicals canform a cyclohexane.

Among the diphosphines corresponding to formula (I), the differentradicals represent more particularly:

for the R₁ and R₂ radicals,

a hydrogen atom,

a linear or branched alkyl radical having from 1 to 4 carbon atoms,

for the R₃ radical,

a radical other than a hydrogen atom, preferably a linear or branchedalkyl radical having from 1 to 4 carbon atoms, a phenyl radical,

and for the R₄ and R₅ radicals,

a hydrogen atom,

a linear or branched alkyl radical having from 1 to 4 carbon atoms,

a phenyl radical or a phenyl radical carrying one or more substituents,preferably 1 to 3 linear or branched alkyl or alkoxy radicals having 1to 4 carbon atoms, a naphthyl radical,

R₄ and R₅ cannot simultaneously represent a phenyl group.

In its preferred form, the invention relates to new diphosphinescorresponding to formula (I′) in which the R₅ radical can represent asterically hindered group such as a substituted phenyl radical or atertiary radical, i.e. the carbon atom located in b position withrespect to the phosphorus atom carries three substituents (for example atert-butyl radical).

By sterically hindered group is understood a group having a stericalhindrance greater than that of a phenyl radical and which can bedetermined by the molecular volume.

For the determination of the molecular volume, reference can be made tothe data in the literature and in particular to the articles A.Gavezotti, J. Am. Chem. Soc., 105, 5220 (1983) and M. L. Connolly, J.Am. Chem. Soc., 107, 1118 (1985).

Thus, the diphosphines corresponding more particularly to the followingformula (I′) show specific characteristics:

in said formula (I′):

R₁, R₂, R₃, R₄, identical or different, represent a hydrogen atom or ahydrocarbon radical, optionally substituted, having from 1 to 40 carbonatoms, which can be a saturated or unsaturated, linear or branchedacyclic aliphatic radical; a saturated, unsaturated or aromatic,monocyclic or polycyclic, carbocyclic or heterocyclic radical; asaturated or unsaturated, linear or branched aliphatic radical carryinga cyclic substituent,

R₂ and R₃ can form together with the carbon atoms which carry them asaturated or unsaturated ring,

R₅ represents a saturated or unsaturated branched aliphatic radical thecharacteristic of which is having a tertiary radical located in bposition with respect to the phosphorus atom and there can in particularbe mentioned a tert-butyl radical; a phenyl radical carrying at leastone substituent, preferably one or more alkyl or alkoxy radicals havingfrom 1 to 4 carbon atoms or a naphthyl radical,

R₄ and R₅ cannot simultaneously represent a phenyl group.

Diphosphines of Formula (I)

Another subject of the invention relates to the preparation process fordiphosphines of formula (I) characterized in that it consists inreacting:

a diphosphole of formula (III) originating from the rearrangement of thediphosphole of formula (IV):

in said formulae (III) and (IV), R₁, R₂ and R₃ have the meaningindicated previously,

and an acetylenic compound of formula (V):

in said formula (V), R₄ and R₅ have the meaning given previously.

The diphosphines of formula (I) are therefore obtained by reactionbetween a diphosphole of formula (III) and an acetylenic compound offormula (V).

The diphospholes of formula (III) are prepared from diphospholes offormula (IV) according to a rearrangement obtained by thermal treatmentcarried out at a temerature comprised between 100° C. and 200° C.,preferably between 130° C. and 150° C.

As diphospholes of formula (IV) preferentially implemented, there can bementioned:

1,1′-bis-(3,4-dimethylphosphole),

1,1′-bis-(3-methylphosphole),

1,1′-bis-(phosphole).

As regards the acetylenic compound of formula (V), use is preferentiallymade of:

acetylene,

methylacetylene,

tert-butylacetylene,

phenylacetylene,

phenylmethylacetylene,

o-tolylacetylene,

bis-(o-tolylacetylene),

phenyl-tert-butylacetylene,

phenylmesitylacetylene,

bis-(mesityl)acetylene.

The acetylenic compounds of formula (V) are products which can beobtained according to the processes described in the literature [inparticular Journal of the American Chemical Society 95, p. 3080-3081(1973) and J. Org. Chem. 36, p. 3520 et seq. (1971)].

The quantity of acetylenic compound of formula (V) expressed in moles ofacetylenic compound per mole of diphosphole of formula (IV) can alsovary within wide limits. The acetylenic compound of formula(V)diphosphole of formula (IV) molar ratio can vary between 1 and 4,preferably between 1 and 1.5.

The reaction is advantageously carried out without a solvent. However,it is desirable to use an organic solvent, preferably apolar, aproticwhen one wishes to solubilize the acetylenic compound.

As examples of solvents suitable for the present invention, there can inparticular be mentioned the aliphatic, cycloaliphatic or aromatichydrocarbons.

As examples of aliphatic or cycloaliphatic hydrocarbons, there can bementioned more particularly paraffins such as in particular hexane,heptane, octane, nonane, decane, undecane, dodecane, tetradecane,cyclohexane, aromatic hydrocarbons such as in particular benzene,toluene, xylenes, cumene, petroleum cuts constituted by a mixture ofalkylbenzenes, in particular cuts of Solvesso® type.

The preferred solvents are toluene and xylenes.

A mixture of organic solvents can also be used.

The highest possible concentration of diphosphole in the medium isselected. It is most often comprised between 1 and 25 mol per liter ofmedium and, preferably, between 5 and 10 mol per liter.

The reaction temperature is as stated previously, between 100° C. and200° C., preferably between 130° C. and 150° C.

Generally, the reaction is carried out under atmospheric pressure, buthigher pressures can also be suitable, ranging from 1 to 50 bar,preferably from 1 to 25 bar. The process is carried out under autogenouspressure when the reaction temperature is greater than the boiling pointof the reagents and/or the products.

It is preferred to carry out the reaction under a controlled atmosphereof inert gases such as nitrogen or the rare gases, for example argon.

The duration of the reaction can be very variable. It is most frequentlybetween 15 minutes and 10 hours, preferably between 30 minutes and 5hours.

From a practical point of view, the process can be implementeddiscontinuously or continuously.

A practical implementation consists of loading the diphosphole offormula (IV), the acetylenic compound of formula (V) preferably dilutedin the organic solvent. The inert gas atmosphere is established followedby heating under a closed atmosphere.

At the end of the reaction, a mixture of two diastereoisomers isobtained, a diphosphine in meso form (lm) and a diphosphine in racemicform (lr):

in the formulae (lm) and (lr), the different symbols have the meaninggiven previously.

Diphospholes of Formula (IV)

A method of accessing the compounds of formula (IV) used as startingreagents for the preparation of the diphosphines relates to a processwhich consists in reacting:

a compound of formula (VI):

in formula (VI), R₁, R₂, R₃ have the meanings indicated previously, andY represents any group, preferably an aromatic carbocyclic radical, andmore preferentially, a phenyl radical or an aromatic heterocyclicradical,

with an alkali metal, leading to a compound of formula (VII):

in formula (VII), R₁, R₂, R₃ have the meanings indicated previously, andM represents an alkali metal, preferably lithium or sodium.

dimerizing the compound of formula (VII) into a compound of formula(IV).

The phosphole of formula (VI) is reacted with an alkali metal which canbe sodium or any other alkali metal, but more preferentially lithium.

The metal is generally in excess. Thus the ratio between the number ofgram-atoms of alkali metal and the number of moles of compound offormula (VI) advantageously varies between 2 and 3.

The compound of formula (VI) and the alkali metal are reacted at atemperature comprised between 10° C. and 40° C., preferably between 10°C. and 20° C.

The reaction generally lasts between 30 minutes and 2 hours.

The reaction is advantegously carried out in an organic solvent,preferably an aprotic polar solvent. There can in particular bementioned aliphatic, cycloaliphatic or aromatic ether oxides and, moreparticularly, diethyl oxide, dipropyl oxide, diisopropyl oxide, dibutyloxide, methyltertiobutylether, dipentyl oxide, diisopentyl oxide,ethyleneglycol dimethylether (or 1,2-dimethoxyethane), diethyleneglycoldimethylether (or 1,5-dimethoxy 3-oxapentane); benzyl oxide; dioxane,tetrahydrofuran (THF).

Among said solvents, tetrahydrofuran is preferentially used.

The quantity of organic solvent used can vary very widely. The ratiobetween the number of moles of solvent and the number of moles ofsubstrate can thus range from 10 to 40 and is preferably comprisedbetween 20 and 25.

A preferred variant consists of trapping the YM compound which hasformed. For this purpose, a Lewis acid is used, preferably AlCl₃ andoptionally a tertiary alkyl halide, preferably tert-butyl chloride.

Said reagents are used in an equal quantity or a quantity close to thestoichiometric quantity.

From a practical point of view, there are no constraints to be observed.The phosphole of formula (VI) can be loaded, with excess alkali metal.

The reaction is left to run for 30 minutes to 2 hours.

The excess metal is eliminated (solid/liquid separation), then Lewisacid and/or tertiary alkyl halide is added, between 0° C. and 20° C.

In the following stage, the compound of formula (VII) is dimerized.

The iodine is preferentially used as coupling agent, preferably used ina stoichiometric quantity.

The reaction is generally carried out in the same type of organicsolvent as in the previous stage.

The reaction is carried out at ambient temperature (generally between15° C. and 25° C).

The diphosphole of formula (IV) is obtained.

Phospholes of Formula (VI)

The compound of formula (VI) can be obtained by reacting a diene offormula (VIII) with a dihalogenarylphosphine:

in formula (VIII), R₁, R₂, R₃ have the meanings given previously.

As examples of dihalogenarylphosphines used, use is generally made ofdichlorophenylphosphine, dibromophenylphosphine or their mixturespreferably comprising equimolar quantities of each of thedihalogenphosphines.

The compound of formula (VIII) and dihalogenarylphosphine are mixed,used in stoichiometric or similar quantities.

According to a practical implementation, the dienic compound of formula(VIII) is reacted with dihalogenarylphosphine, generally solubilized inan appropriate solvent, preferably an aliphatic or aromatic halogenatedhydrocarbon.

There can more particularly be mentioned dichloromethane,1,2-dichloroethane; monochlorobenzene, 1,2-dichlorobenzene,1,3-dichlorobenzene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene ormixtures of different chlorobenzenes; monobromobenzene or mixtures ofmonobromobenzene with one or more dibromobenzenes; 1-bromonaphthalene.

Dichloromethane is more preferentially chosen.

The concentration of dihalogenarylphosphine in the medium can varywithin wide limits. It can thus be comprised between 5 and 20 mol perliter of medium and, preferably, is approximately 10 mol per liter.

The reaction is advantageously carried out between 0° C. and 20° C.,preferably sheltered from the air. It lasts from one to several days,for example 15 days.

At the end of the reaction, a phospholenium salt is obtained (P⁺X⁻).

The phosphole of formula (VI) results from the elimination of 2 moles ofHX per mole of dihalogenarylphosphine, which is carried out in thepresence of an amine, preferably a tertiary amine.

As more specific examples, there can be mentioned picolines, pyridine,2-ethylpyridine, 4-ethylpyridine, 2-methylpyridine, 4-methylpyridine,2,6-dimethylpyridine, imidazole, 1-methylimidazole, TMEDA(tetramethylenediamine), N-methylpyrrolidine, 4-methylmorpholine,triethylamine, DBU (1,8-diazabicyclo[5.4;0.]undecene-7).

The quantity of amine is generally equal to twice the stoichiometricquantity of dihalogenarylphosphine, i.e. 2 or 3 times in excess of thestoichiometry.

The reaction is advantageously carried out in a mixture of two organicsolvents, one solubilizing the phosphole obtained, the othersolubilizing the amine salts formed in order to facilitate subsequentseparation.

As examples of solvents suitable for extracting the phosphole obtained,there can be mentioned in particular the aliphatic, cycloaliphatic oraromatic hydrocarbons. For examples, reference can be made to the listgiven previously.

As regards the solubilization of the amine salts obtained, use can bemade of, among others, aliphatic or aromatic halogenated hydrocarbons,as previously mentioned.

The preferred pair of solvents is hexane and dichloromethane preferablyused in similar or equal volumes.

The concentration of diphosphole in the medium can vary within widelimits. It can thus be comprised between 1 and 5 mol per liter of mediumand, preferably between 2 and 3 mol per liter.

A mixture of organic solvents as indicated above and a base, preferablyan amine, are then introduced.

At the end of the reaction, if necessary, the excess amine isneutralized with an acid solution, preferably a mineral acid solution,such as for example hydrochloric acid.

The organic phases are then separated.

It is possible to subject the organic phase containing the amine saltsto a standard treatment in order to recover the phosphole it maycontain.

The treatment consists of extraction with a solvent of the phosphole,washing the organic phase, generally with water and frequently followedby standard drying over a desiccant, for example sodium or magnesiumsulphate.

The organic phases containing the phosphole are combined, then, afterevaporation of the solvent, a phosphole of formula (VI) is recovered.

Diphosphine Dioxides in Meso or Racemic Form

Another subject of the invention relates to diphosphine dioxides in mesoand racemic form as well as the process for obtaining them.

In fact, according to what is described in the state of the art, it isimpossible in the context of the preparation of all the diphosphines offormula (I) to separate the two diastereoisomers by forming a palladiumchelate (II).

It has thus been found that the diastereoisomers could be separatedaccording to a process which consists in subjecting the mixture ofdiastereoisomers to an oxidization reaction thus converting them intodiphosphine dioxides, then separating the diphosphine dioxides into thetwo diastereoisomers.

According to a first operation, the diastereoisomers are converted intooxide form.

They can be symbolized by the following formula:

in formula (IX), the different symbols have the meaning givenpreviously.

The diphosphine oxides of formula (IX) are obtained by oxidizing the twodiastereoisomers of formula (lm) and (lr) using an oxidizing agent.

Although it is possible to use any type of oxidizing agent, a chemicaloxidant, for example potassium permanganate or molecular oxygen or a gascontaining same, it is preferable to use hydrogen peroxide, preferablyin the form of an aqueous solution.

The concentration of the hydrogen peroxide solution is advantageouslycomprised between 10% and 35% by weight.

The quantity of oxidizing agent used can vary widely from thestoichiometric quantity up to an excess representing for example 20times the stoichiometry.

Use is made of an organic solvent which solubilizes all the reagents.The solvent can be chosen from the aliphatic, cycloaliphatic or aromatichydrocarbons, preferably aromatic. Examples are given above.

Among all these solvents, toluene and xylenes are preferred.

The concentration of the diphosphine in the reaction solvent ispreferably between 0.05 and 1 mole/liter and even more particularlybetween 0.05 and 0.2 mole/liter.

The diastereoisomers are therefore brought into contact, generallydissolved in an appropriate solvent, in contact with the oxidizingagent.

The reaction is advantageously carried out between 50° C. and 100° C.

The duration of the reaction is generally between 30 minutes and 4hours.

Diphosphine oxidies are recovered in the organic phase.

The aqueous and organic phases are separated.

The phases are treated in a standard manner.

The aqueous phase is thus washed several times (from 1 to 3) with anorganic solvent for the extraction of diphosphine oxides, for exampleethyl ether.

All the organic phases are combined and washed with salt water(saturated solution of sodium chloride) preferentially followed bystandard drying operation over a desiccant, for example sodium ormagnesium sulphate.

In a following stage, the oxides of the two diastereoisomers areseparated.

The solvent is concentrated by evaporation, then the separation iscarried out in a known manner [A. Bertheillier—Dunod Paris (1972)] byliquid column chromatography, preferably with a silica support.

The column is eluted with a mixture of appropriate solvents.

Suitable solvents for separation are determined by simple operationsexecuted by a person skilled in the art which consist in carrying outchromatography on a silica plate.

The solvents are generally chosen from ethyl acetate, methanol, ethylether or their. mixtures.

Thus, depending on the case, the following are recovered from theelution solvents in a variable order: diphosphine dioxide in meso form(IXm) and diphosphine dioxide in racemic form (IXr).

in formulae (IXm) and (IXr), the different symbols have the meaningsgiven previously.

Diphosphine Disulphides in Racemic or Meso Form

Another subject of the invention relates to diphosphine disulphides inmeso and racemic form as well as the process for obtaining them.

It has also been found that the diastereoisomers could be separatedaccording to a process which consists in reacting the mixture ofdiastereoisomers (lm) and (lr) with sulphur, thus converting them intodiphosphine disulphlides (IX′m) and (IX′r), then separating the twodiastereoisomers of the diphosphine disulphides.

According to a first operation, the diastereoisomers are converted intosulphide form.

They can be symbolized by the following formula:

in formula (IX′), the different symbols have the meaning givenpreviously.

The sulphur (S₈) is thus reacted with the mixture of twodiastereoisomers in meso form (lm) and in racemic form (lr) leading to amixture of diphosphine disulphides, in meso or racemic form.

The quantity of sulphur used defined with respect to each phosphorusatom generally varies from the stoichiometric quantity up to a slightexcess of 10%.

The reaction takes place at a temperature ranging from ambienttemperature to approximately 100° C., preferably in the region of 80°C., in a solvent preferably of aromatic hydrocarbon type, and inparticular toluene.

In a following stage, the mixture of diastereoisomers is separated on asilica column as previously described.

The diphosphine disulphide is thus recovered in meso form (IX′m) and thediphosphine disulphide is recovered in racemic form (IX′r):

Diphosphines in Enantiomeric Form

Another subject of the present invention is optically active6,6′-bis-(1-phosphanorbornadiene) diphosphines corresponding to thefollowing formulae:

in formulae (Ia) and (Ib), the different symbols have the meaning givenpreviously.

The invention therefore provides diphosphines which are chiral onphosphorus and non racemiable.

A first variant for obtaining an optically active diphosphine of formula(Ia) or (Ib) consists in resolving the diphosphine dioxide in racemicform (IXr) then separately reducing the diphosphine dioxide enantiomersobtained (IXa) or (IXb).

Another variant of the invention consists in first reducing thediphosphine dioxide in racemic form (IXr) into a diphosphine in racemicform (Ir), then resolving the diphosphine in racemic form (Ir) intoenantiomers (Ia) and (Ib).

Another variant of the invention consists in resolving the racemicmixture of diphosphine disulphides (IX′r) preferably on a chiral columnthen reducing the diphosphine disulphide enantiomers (IX′a) an (IX′b)into diphosphine enantiomers (Ia) and (Ib).

Another variant consists in reducing the racemic mixture of diphosphinedisulphides (IX′r) into the diphosphine racemic mixture (Ir) thenresolving the racemic diphosphine mixture into enantiomers (Ia) and(Ib).

Another variant of the invention of the invention is to convert theracemic mixture of diphosphine disulphides (IX′r) into a racemic mixtureof diphosphine dioxides (IXr) and then obtaining optically activediphosphines (Ia) and (Ib) according to the methods previouslydescribed.

According to a first implementation of the invention, the racemicmixture of diphosphine dioxides (IXr) is resolved. The resolution can becarried out by separating the two enantiomers, by chiral liquidchromatography. A chiral column is used, for example Chirosebond C1®(chiral polymer graft of starch hydrolysate type on spherical silica 5mm-100 Å) and the elution solvents can in particular be awater/acetonitrile mixture.

In this way, two enantiomers are obtained:

in formulae (IXa) and (IXb), the different symbols have the meaninggiven previously.

In a following stage, the optically active diphosphine dioxides offormula (IXa) or (IXb) are reduced. Reference can be made to thedescription of the reduction operation given hereafter.

Another variant first consists in reducing the diphosphine dioxide inracemic form then resolving the diphosphine in racemic form obtained.

The reduction can be carried out with a reduction agent such as forexample trichlorosilane, hexachlorodisilazane, plhenyltrisilane, ahydride in particular LiAlH₄ or NaBH₄.

The quantity of reducing agent used can vary widely from thestoichiometric quantity to an excess representing for example 20 timesthe stoichiometry.

When a reducing agent is used which leads to the release of ahalogenated acid, for example trichlorosilane or hexachlorosilazane, abase is added, preferably an amine so that it traps the halogenated(hydrochloric) acid released.

As more specific examples, there can be mentioned picolines, pyridine,2-ethylpyridine, 4-ethylpyridine, 2-methylpyridine, 4-methylpyridine,2,6-dimethylpyridine, imidazole, 1-methylimidazole, TMEDA(tetramethylenediamine), N-methylpyrrolidine, 4-methylmorpholine,triethylamine, DBU (1,8-diazabicyclo[5.4;0.]undecene-7).

The quantity of amine is at least equal to the quantity necessary totrap the halogenated acid released and is more generally in excess, ofup to 3 times the stoichiometric quantity.

The reaction is carried out in an organic solvent which solubilizes allthe reagents. The solvent can be chosen from aliphatic, aromatic,halogenated or non-halogenated hydrocarbons.

Among all these solvents, toluene and dichloromethane are preferred.

The concentration of diphosphine in the reaction solvent is preferablybetween 0.05 and 1 mole/liter and even more particularly between 0.05and 0.2 mole/liter.

From a practical point of view, in a mixture of solvents and in thepresence of an amine, the racemic compound is generally added in theform of oxides followed by the reducing agent.

The reaction is advantageously carried out between 50° C. and 100° C.

The duration of the reaction is generally between 30 minutes and 4hours.

The racemic mixture is in organic phase.

It is sometimes necessary to carry out basic treatment where thereducing agent is in excess in order to destroy it.

After cooling down, a base is then added, preferably soda, potash orsodium carbonate, until a basic pH is obtained (pH of at least 8).Preferably, a basic aqueous solution is used, preferably a soda solutionhaving a concentration of 10% to 30%.

The aqueous and organic phases are separated.

The diphosphine enantiomers are recovered from the organic phase whichis subjected to standard treatment as described previously, extractionwith a solvent, washing with salt water and optionally drying.

A racemic mixture of the two enantiomers is obtained which can then beseparated.

In this way, according to the process of the invention, there followsthe separation of a meso compound (lm) and a racemic compound (lr),which are also new products.

According to another subject of the invention, the racemic mixture of6,6′-bis-(1-phosphanorbornadiene) is resolved according to a processwhich consists in reacting it with a palladium and/or platinum complexas chiral auxiliary, in an organic solvent thus formingdiastereoisomeric complexes, then resolving said optically purecomplexes.

In conformity with the process of the invention, use is made of apalladium complex. This type of chiral auxiliary is widely described inthe literature, in particular by Sei Otsuka et al., in Journal of theAmerican Chemical Society 93, pp. 4301 (1971).

Use can also be made of a platinum complex and more particular referencecan be made to the works of A. C. Cope [Journal of the American ChemicalSociety 90, pp. 909 (1968)].

The chiral complex used corresponds more particularly to general formula(X):

in said formula:

M represents palladium and/or platinum,

R₁, R₂, R₃ and R₄ represent a hydrogen atom or an alkyl radical havingfrom 1 to 10 carbon atoms or a cycloalkyl radical having from 3 to 10carbon atoms,

R₃ and R₄ are different and at least one of the two represents ahydrogen atom,

R has the meaning given for R₁, R₂, R₃ and R₄,

X represents a halogen atom,

n is a number from 0 to 4,

when n is greater than 1, two R radicals and the 2 successive atoms ofthe benzene ring can together form a ring having from 5 to 7 carbonatoms.

More preferentially, the complex used corresponds to the aforementionedformula in which R₁, R₂, R₃ and R₄ represent a hydrogen atom or a methylradical, X represents a chlorine atom and n is equal to 0.

When n is equal to 2, two R radicals form a benzene ring.

As more specific examples of palladium complexes suitable for thepresent invention obtained either from (R)-(+) or(S)-(−)-N,N-dimethylphenylethylamine, there can be mentioned:

The quantity of the aforementioned metal complex expressed in metal isgenerally from 0.5 to 1 atom of metal per atom of phosphorus.

Use is made of an organic solvent which solubilizes all the reagents.The solvent must be inert vis-á-vis the diphosphine.

As non-limitative examples of solvents which are suitable for theinvention process, there can be mentioned aliphatic or aromatic,halogenated or non-halogenated hydrocarbons as mentioned previously.

Among all these solvents, benzene and toluene are preferred.

The concentration of diphosphine in the reaction solvent is preferablybetween 0.05 and 1 mole/liter and even more particularly between 0.05and 0.2 mole/liter.

Separation is advantageously carried out at ambient temperaturegenerally comprised between 15° C. and 25° C.

It preferably occurs under a controlled atmosphere of inert gases. Anatmosphere of rare gases can be established, preferably argon but it ismore economical to use nitrogen.

A mixture of complexes of palladium or platinum and diphosphine isobtained corresponding to each enantiomer.

Another subject of the invention is intermediate products, namelymetallic complexes with diphosphines. According to the nature of thesubstituents, in particular the R₅ radical, complexes of the two formsare obtained either corresponding to formulae (XIIa) and (XIIb) or toformulae (XIIIa) and (XIIIb):

in said formulae, M represents palladium or platinum, X represents ahalogen atom, preferably chlorine and A symbolizes the remainder of achiral metallic complex corresponding to one of formulae (X) andpreferentially (XI).

In a following stage, the two enantiomers are recovered.

Concentration is carried out by evaporation of the solvent, thenseparation is carried out in a known manner [A. Bertheillier—Dunod Paris(1972)] using liquid column chromatography, preferably with a silicasupport.

The column is eluted with a mixture of appropriate solvents.

The solvent or a mixture of solvents is chosen in a standard manner by aperson skilled in the art. Ethyl acetate, methanol, hexane, cyclohexaneor dichloromethane are generally used as solvents. The examplesillustrate the use of a mixture of solvents.

The two isolated enantiomers are recovered in the form of twodiastereoisomeric complexes.

The two enantiomers of the diphosphines are recovered by carrying outdecomplexing.

For this purpose, a hydrocyanic acid salt is particularly used,preferably an alkaline salt and even more preferentially sodium: saidsalt being dissolved in the minimum amount of water required.

The complexes are solubilized in an organic solvent such as, forexample, dichloromethane, then the hydrocyanic acid salt is introducedunder agitation, generally used in an excess representing from 2 to 5mol per atom of metal.

The operation is also carried out under a controlled atmosphere and atambient temperature.

The enantiomer is recovered from the organic phase, which is separated,washed with water and dried, for example over sodium sulphate.

Two 6,6′-bis-(1-phosphanorbornadiene) enantiomers are obtained, isolatedcorresponding to the aforementioned formulae (Ia) and (Ib).

When the optically active diphosphines are prepared according to asulphur route, the racemic mixture of diphosphine disulphides (IX′r) isresolved on a chiral column, resulting in optically active diphosphinedisulphides (IX′a) and (IX′b), then they are reduced to disphosphines,thus leading to optically active diphosphines (Ia) and (Ib).

The diphosphine disulphides are reduced by reaction with a phosphoratedreagent of PBu₃ or P(CH₂CH₂CN)₃ type: the reaction being carried out inan organic solvent medium, for example an aromatic hydrocarbon,preferably toluene.

The reaction is generally carried out at the reflux temperature of thereaction solvent.

In this way, two enantiomers are obtained:

in formulae (IX′a) and (IX′b), the different symbols have the meaninggiven previously.

Another variant consists of reducing the racemic mixture of diphosphinedisulphides (IX′r) into a racemic mixture of diphosphines (Ir) thenresolving the racemic mixture of diphosphines into optically activephosphines (Ia) and (Ib).

The reduction of the racemic mixture of diphosphine disulphides iscandied out in the manner as specified for optically active diphosphinedisulphides.

Finally, another variant of the invention consists of converting theracemic mixture of diphosphine disulphides (IX′r) into a racemic mixtureof diphosphine dioxides (IXr) then obtaining the optically activediphosphines (Ia) and (Ib) according to the routes specified above.

It is possible to convert the diphosphine disulphides into diphosphinedioxides by any appropriate means, in particular by reacting thediphosphine disulphides with cyclohexene oxide, in trifluoroacetic acidand in an organic solvent medium, in particular in a halogenatedaliphatic hydrocarbon, preferably methylene chloride.

The racemic mixture (IXr) is obtained, which is treated as mentionedpreviously.

The optically active diphosphines according to the present invention areof quite particular use in organic chemistry, in asymmetrical synthesisprocesses.

The optically active diphosphines according to the invention can be usedfor the preparation of metallic complexes, allowing asymmetricalhydrogenation of unsaturated derivatives or allylic substitution(Tsuji-Trost type reaction).

More particularly, they can be used to carry out asymmetricalhydrogenation reactions.

The optically active diphosphines according to the invention can be usedfor the preparation of metallic complexes allowing asymmetricalhydrogenation of a,b-unsaturated carboxylic acids and/or derivatives.

The optically active diphosphines of formula (Ia) or (Ib) serve asligands in the formation of complex coordinates with transition metals.

A subject of the invention is therefore new complexes which comprise anoptically active diphosphine and a transition metal which arecharacterized in that the ligand corresponds to one of the followingformulae (Ia) or (Ib).

As examples of transition metals capable of forming complexes, there canin particular be mentioned metals such as rhodium, ruthenium, rhenium,iridium, cobalt, nckel, platinum, palladium.

Among the above metals, rhodium, ruthenium and iridium are preferred.

Specific examples of said complexes of the present invention are givenbelow, without any limitative character.

In said formulae, (P*P) represents the diphosphine of formula (Ia) or(Ib).

The rhodium and iridium complexes can be represented by the followingformulae:

[ML₂(P*P)]Y(XIVa)

[ML₂(P*P)]Y(XIVb)

in said formulae:

(P*P) in formula (XIVa) represents the diphosphine of formula (Ia) andin formula (XIVb) represents the diphosphine of formula (Ib),

M represents rhodium or iridium,

Y represents a coordinating anionic ligand,

L represents a neutral ligand.

The preferred rhodium or iridium complexes correspond to formula (XIVa)or (XIVb) in which:

L represents an olefine having from 2 to 12 carbon atoms and two ligandsL can be linked together to form a polyunsaturated, linear or cyclichydrocarbon chain; L preferably representing 1,5-cyclooctadiene,norbornadiene, ethylene,

Y represents a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻,ClO₄ ⁻, CN⁻, CF₃SO₃ ⁻ anion, preferably halogen, Cl⁻ or Br⁻, a1,3-diketonate, alkylcarbonate, haloalkylcarboxylate anion with a loweralkyl radical, a phenylcarboxylate or phenolate anion the benzene ringof which can be substituted by lower alkyl radicals and/or halogenatoms.

By lower alkyl radicals is generally understood a linear or branchedalkyl radical having from 1 to 4 carbon atoms.

Other iridium complexes can be represented by the formulae:

[IrL(P*P)]Y(XVa)

[IrL(P*P)]Y(XVb)

in said formulae, (P*P), L and Y have the meanings given for formulae(XIVa) and (XIVb).

As regards the ruthenium complexes, they preferentially correspond tothe following formulae:

[RuY₁Y₂(P*P)](XVIa)

[RuY₁Y₂(P*P)](XVIb)

in said formulae:

(P*P) in formula (XVIa) represents the diphosphine of formula (Ia) andin formula (XVIb) represents the diphosphine of formula (Ib),

Y₁ and Y₂, identical or different, preferably represent a PF₆ ⁻, PCl₆ ⁻,BF₄ ⁻, BCl₄ ⁻, SbF₆ ⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄ ⁻, CF₃SO₃ ⁻anion, a halogenatom, more particularly chlorine or bromine or a carboxylate anion,preferentially acetate, trifluoroacetate.

Other ruthenium complexes which may be used in the process according tothe invention correspond to the following formulae:

[RuY₁Ar(P*P)Y₂](XVIc)

 [RuY₁Ar(P*P)Y₂](XVId)

in said formulae:

(P*P) in formula (XVIc) represents the diphosphine of formula (Ia) andin formula (XVId) represents the diphosphine of formula (Ib),

Ar represents benzene, p-methylisopropylbenzene, hexamethylbenzene,

Y₁ represents a halogen atom, preferably chlorine or bromine,

Y₂ represents an anion, preferably a PF₆ ⁻, PCl₆ ⁻, BF₄ ⁻, BCl₄ ⁻, SbF₆⁻, SbCl₆ ⁻, BPh₄ ⁻, ClO₄ ⁻, CF₃SO₃ ⁻ anion.

It is also possible to use palladium- and platinum-based complexes inthe process of the invention.

As more specific examples of said complexes, there can be mentionedamong others PdCl₂(P*P) and PtCl₂(P*P) in which (P*P) represents thediphosphine of formula (Ia) or (Ib).

The complexes comprising the aforementioned diphosphine and thetransition metal can be prepared according to known processes describedin the literature.

For the preparation of ruthenium complexes, reference can be made inparticular to the publication of J.-P. Genêt [Acros Organics Acta,1, No.1, pp. 1-8 (1994)] and for the other articles, reference can be made tothe article by Schrock R. and Osborn J. A. [Journal of the AmericanChemical Society, 93, pp. 2397 (1971)].

They can be prepared in particular by reacting the diphosphine offormula (Ia) or (Ib) with the transition metal compound, in anappropriate organic solvent.

The reaction is carried out at a temperature comprised between ambienttemperature (from 15 to 25° C.) and the reflux temperature of thereaction solvent.

As examples of organic solvents, there can be mentioned among othersaliphatic, halogenated or non-halogenated hydrocarbons and moreparticularly hexane, heptane, isooctane, decane, benzene, toluene,methylene chloride, chloroform; solvents of ether or ketone type and inparticular diethylether, tetrahydrofuran, acetone, methylethylketone;solvents of alcohol type; preferably methanol or ethanol.

The metallic complexes according to the invention, recovered accordingto standard techniques (filtration or crystallization) are used inasymmetrical hydrogenation reactions of substrates specified below.

Another subject of the present invention is to provide a preparationprocess for an optically active carboxylic acid and/or derivative, whichprocess is characterized by the fact that asymmetrical hydrogenation iscarried out on an a,b-unsaturated carboxylic acid and/or its derivativesin the presence of an effective quantity of a metallic complexcomprising as ligand the optically active diphosphine of formula (Ia) or(Ib) and a transition metal.

The a,b-unsaturated carboxylic acid and/or its derivatives correspondmore particularly to formula (XVII):

in said formula (XVII):

R₁, R₂, R₃ and R₄ represent a hydrogen atom and any hydrocarbon group,provided that:

if R₁ is different from R₂ and different from a hydrogen atom, then R₃can be any hydrocarbon or functional group designated by R.

if R₁ or R₂ represents a hydrogen atom and if R₁ is different from R₂,then R₃ is different from a hydrogen atom and different from —COOR₄,

if R₁ is identical to R₂ and represents any hydrocarbon or functionalgroup designated by R then R₃ is different from —CH—(R)2 and differentfrom —COOR₄,

one of groups R₁, R₂ and R₃ can represent a functional group.

The identical or different R₁ to R₄ radicals represent an optionallysubstituted hydrocarbon radical having from 1 to 20 carbon atoms, whichcan be a saturated or unsaturated, linear or branched acyclic aliphaticradical; a saturated, unsaturated or aromatic, monocyclic or polycyclic,carbocyclic or heterocyclic radical; a saturated or unsaturated, linearor branched aliphatic radical carrying a cyclic substituent.

In general formula (XVII), R₁ to R₄, identical or different, can assumevarious meanings. Different examples are given below but are in no waylimitative.

The R₁ to R₄ radicals thus preferentially represent an aromatichydrocarbon radical, and in particular benzenic, corresponding togeneral formula (XVIII):

in said formula (XVIII):

n is an integer from 0 to 5, preferably 0 to 3,

Q represents R₀, one of the following groups or functions:

a linear or branched alkyl radical having from 1 to 6 carbon atoms,preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,

a linear or branched alkenyl radical having from 2 to 6 carbon atoms,preferably 2 to 4 carbon atoms, such as vinyl, allyl,

a linear or branched alkoxy radical having from 1 to 6 carbon atoms,preferably from 1 to 4 carbon atoms such as the methoxy, ethoxy,propoxy, isopropoxy, butoxy radicals,

an acyl group having from 2 to 6 carbon atoms,

a radical of formula:

—R₅—OH

—R₅—COOR₇

—R₅—CHO

—R₅—NO₂

—R₅—CN

—R₅—N(R₇)₂

—R₅—CO—N(R₇)₂

—R₅—SH

—R₅—X

—R₅—CF₃

in said formulae, R₅ represents a valency bond or a linear or branched,saturated or unsaturated divalent hydrocarbon radical having from 1 to 6carbon atoms such as, for example, methylene, ethylene, propylene,isopropylene, isopropylidene; R₇ represents a hydrogen atom or a linearor branched alkyl radical having from 1 to 6 carbon atoms; X representsa halogen atom, preferably a chlorine, bromine or fluorine atom,

Q represents R₀′, one of the following more complex radicals:

in which:

m is an integer from 0 to 5, preferably from 0 to 3,

R₀ has the meaning given previously,

R₆ represents a valency bond; a linear or branched, saturated orunsaturated divalent hydrocarbon group having from 1 to 6 carbon atomssuch as for example methylene, ethylene, propylene, isopropylene,isopropylidene or one of the following groups referred to as Z:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂—; —NR₇—CO—;

in said formulae R₇ represents a hydrogen atom, a linear or branchedalkyl group having from 1 to 6 carbon atoms, preferably a methyl orethyl radical.

When n is greater than 1, the radicals Q can be identical or differentand 2 successive carbon atoms of the benzene ring can be linked togetherby a ketal bridge such as the extranuclear methylene dioxy or ethylenedioxy radicals.

Preferably, n is equal to 0, 1, 2 or 3.

Among all the aforementioned R₁ to R₄ radicals, the following are quitepreferentially used in the process of the invention: carboxylic acids orderivatives corresponding to general formula (XVII) in which R₁ to R₄represent an aromatic radical corresponding to general formula (XVIII)in which:

n is equal to 0, 1,2 or 3,

Q represents one of the following groups or functions:

a hydrogen atom,

a linear or branched alkyl radical having from 1 to 4 carbon atoms,

a linear or branched alkoxy radical having from 1 to 4 carbon atoms,

a benzoyl group,

an —OH group,

a —CHO group,

an NH₂ group,

an NO₂ group,

a phenyl radical,

a halogen atom,

a CF₃ group.

Even more preferentially, the compounds of formula (XVII) are chosen inwhich the Q radicals, identical or different, are a hydrogen atom, analkyl radical having from 1 to 4 carbon atoms, a methoxy radical, abenzoyl group, an NO₂ group.

As examples of R₁ to R₄ radicals corresponding to formula (XVII), therecan more specifically be mentioned the phenyl, tolyl or xylyl,1-methoxyphenyl, 2-nitrophenyl radicals and the biphenyl,1,1′-methylenebiphenyl, 1,1′-isopropylidenebiphenyl,1,1′-carboxybiphenyl, 1,1′-oxybiphenyl, 1,1′-iminobiphenyl radicals:said radicals being able to be substituted by one or more Q radicals asdefined previously.

R₁ to R₄ can also represent a polycyclic aromatic hydrocarbon radical;the rings together being able to form ortho-condensed, ortho- andperi-condensed systems. There can more particularly be mentioned anaphthalenic radical; said rings being able to be substituted by 1 to 4R₀ radicals, preferably 1 to 3, R₀ having the meanings specifiedpreviously for the substituents of the aromatic hydrocarbon radical ofgeneral formula (XVIII).

In general formula (XVII) for carboxylic acids, R₁ to R₄ can alsorepresent a carbocyclic radical which is saturated or comprises 1 or 2unsaturations in the ring, generally having from 3 to 7 carbon atoms,preferably 6 carbon atoms in the ring; said ring being able to besubstituted by 1 to 5 R₀ radicals, preferably 1 to 3, R₀ having themeanings indicated previously for the substituents of the aromatichydrocarbon radical of general formula (XVIII).

As preferred examples of R₁ to R₄ radicals, there can be mentioned thecyclohexyl or cyclohexene-yl radicals, optionally substituted by linearor branched alkyl radicals, having from 1 to 4 carbon atoms.

As mentioned previously, R₁ to R₄ can represent a saturated orunsaturated, linear or branched acyclic aliphatic radical.

More precisely, R₁ to R₄ represent a linear or branched acyclicaliphatic radical preferably having from 1 to 12 carbon atoms, saturatedor comprising one or more unsaturations on the chain, generally 1 to 3unsaturations which can be single or conjugated double bonds or triplebonds.

The hydrocarbon chain can optionally be:

interrupted by one of the following groups Z:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO—; —NR₇—CO—; in saidformulae,

R₇ represents a hydrogen atom, a linear or branched alkyl group havingfrom 1 to 6 carbon atoms, preferably a methyl or ethyl radical,

and/or carrying one of the following substituents:

—OH, —COOR₇, —CHO, —NO₂, —CN, —NH₂, —SH, —X, —CF₃, in these formulae, R₇has the meaning given previously.

It is also possible to make use of a carboxylic acid or derivative offormula (XVII) in which R₁ to R₄ represent a saturated or unsaturated,linear or branched acyclic aliphatic radical which can optionally carrya cyclic substituent. By ring is understood a saturated, unsaturated oraromatic carbocyclic or heterocyclic ring.

The acyclic aliphatic radical can be linked to the ring by a valencybond or by one of the aforementioned groups Z.

As examples of cyclic substituents, there can be envisagedcycloaliphatic, aromatic or heterocyclic substituents, in particularcycloaliphatic substituents comprising 6 carbon atoms in the ring orbenzene substituents, these cyclic substituents themselves beingoptional carriers of 1, 2, 3, 4 or 5 R₀ radicals, identical ordifferent, R₀ having the meanings indicated previously for thesubstituents of the aromatic hydrocarbon radical of general formula(XVIII).

As examples of such radicals, there can be mentioned, amongst others,the benzyl radical.

In general formula (XVII) for carboxylic acids, R₁ to R₄ can alsorepresent a a saturated or unsaturated heterocyclic radical inparticular comprising 5 or 6 atoms in the ring including 1 or 2heteroatoms such as the nitrogen, sulphur and oxygen atoms; the carbonatoms of the heterocycle being optionally substituted, totally or onlypartially by the R₀ radicals, R₀ having the meanings indicatedpreviously for substituents of the aromatic hydrocarbon radical ofgeneral formula (XVIII).

R₁ to R₄ can also represent a polycyclic heterocyclic radical defined asbeing either a radical constituted by at least 2 aromatic ornon-aromatic heterocycles containing at least one heteroatom in eachring and together forming ortho- or ortho- and peri-condensed systems ora radical constituted by at least one aromatic or non-aromatichydrocarbon ring and at least one aromatic or non-aromatic heterocycletogether forming ortho- or ortho- and peri-condensed systems; the carbonatoms of said rings being optionally substituted, totally or onlypartially, by R₀ radicals, R₀ having the meanings indicated previouslyfor the substituents of the aromatic hydrocarbon radical of generalformula (XVIII).

As examples of R₁ to R₄ groups of heterocyclic type, there can bementioned among others the furyl, pyrrolyl, thienyl, isoxazolyl,furazannyl, isothiazolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrannyl radicals and the quinolyl, naphthyridinyl,benzopyrannyl, benzofurannyl, indolyl radicals.

It is also possible for one of the R₁ to R₃ radicals to represent afunctional group and there can be mentioned in particular the functionalgroups of type NR₉R′₉ in which R₉, R′₉, identical or different,represent a hydrogen atom, a linear or branched alkyl group having from1 to 12 carbon atoms, a phenyl group, a benzyl group or an acyl grouphaving from 2 to 12 carbon atoms, preferably an acetyl or benzoyl group.

As a more specific example, there can be mentioned amongst others2-methyl-2-butenoic acid.

A first class of substrates to which the process of the inventionpreferentially relates is the substituted acrylic acid precursors ofamino acids and/or derivatives.

By substituted acrylic acids is understood all compounds the formula ofwhich derives from that of acrylic acid, substituting up to two hydrogenatoms carried by ethylenic carbon atoms with a hydrocarbon group or witha functional group.

They can be symbolized by the following chemical formula:

in said formula (XVIIa):

R₉, R′₉, identical or different, represent a hydrogen atom, a linear orbranched alkyl group having from 1 to 12 carbon atoms, a phenyl group oran acyl group having from 2 to 12 carbon atoms, preferably an acetyl orbenzoyl group,

R₈ represents a hydrogen atom, an alkyl group having from 1 to 12 carbonatoms, a cycloalkyl radical having from 3 to 8 carbon atoms, anarylalkyl radical having from 6 to 12 carbon atoms, an aryl radicalhaving from 6 to 12 carbon atoms, a heterocyclic radical having from 4to 7 carbon atoms,

R₁₀ represents a hydrogen atom or a linear or branched alkyl grouphaving from 1 to 4 carbon atoms.

As more specific examples of R₈ groups, there can be mentioned an alkylgroup such as methyl, ethyl, isopropyl, isobutyl; a cycloalkyl groupsuch as cyclopentyl, cyclohexyl; an aromatic group such as phenyl,naphthyl or a heterocyclic group such as furyl, pyrannyl, benzopyrannyl,pyrrolyl, pyridyl, indolyl.

The R₁₀ group is preferentially a hydrogen atom.

Among the substituted acrylic acids which are precursors of amino acids,there can be mentioned N-acetyl a-amino b-phenylacrylic acid, N-benzoyla-amino b-phenylacrylic acid, in which the phenyl ring is optionallysubstituted by one or more alkyl, alkoyloxy or hydroxy groups, N-acetyla-amino b-indolylacrylic acid, N-benzoyl a-amino b-indolylacrylic acid,N-acetyl a-amino b-isobutyl acrylic acid.

There can more particularly be mentioned:

methyl a-acetamidocinnamate,

methyl acetamidoacrylate,

benzamidocinnamic acid,

a-acetamidocinnamic acid.

The invention also relates equally well to the hydrogenation of itaconicacid and/or a derivative, and more specifically to compoundscorresponding to formula (XVIIb):

in said formula (XVIIb):

R₁₁, R₁₂, identical or different, represent a hydrogen atom, a linear orbranched alkyl group having from 1 to 12 carbon atoms, a cycloalkylradical having from 3 to 8 carbon atoms, an arylalkyl radical havingfrom 6 to 12 carbon atoms, an aryl radical having from 6 to 12 carbonatoms, an aryl radical having from 6 to 12 carbon atoms, a heterocyclicradical having from 4 to 7 carbon atoms,

R₁₀, R′₁₀, identical or different, represent a hydrogen atom or a linearor branched alkyl group, having from 1 to 4 carbon atoms.

The preferred substrates correspond to formula (XVIIb) in which R₁₁,R₁₂, identical or different, represent a hydrogen atom, an alkyl grouphaving from 1 to 4 carbon atoms and R₁₀, R′₁₀, identical or different,represent a hydrogen atom or a methyl group.

As more specific examples, there can be mentioned in particular itaconicacid and dimethyl itaconate.

The process of the invention relates quite particularly to thepreparation of arylpropionic acids by hydrogenation of a substratecorresponding to formula (XVIIc):

in said formula (XVIIc):

R₁₀ represents a hydrogen atom or a linear or branched alkyl grouphaving from 1 to 4 carbon atoms,

R₁₃ represents a phenyl or naphthyl group, optionally carrying asubstituent or several substituents R:

R can represent R₀, one of the following groups:

a linear or branched alkyl or alkenyl group having from 1 to 12 carbonatoms, preferably a linear or branched alkyl group having from 1 to 4carbon atoms,

a linear or branched alkoxy group having from 1 to 12 carbon atoms,preferably a linear or branched alkoxy group having from 1 to 4 carbonatoms,

a linear or branched acyloxy group having from 2 to 8 carbon atoms,preferably an acetoxy group,

a linear or branched acylamido group having from 1 to 8 carbon atoms,preferably an acetamido group,

an NO₂ group,

R can represent R₀′, one of the following more complex groups:

a group of formula

R₆ represents a valency bond; a linear or branched, saturated orunsaturated divalent hydrocarbon group, such as for example methylene,ethylene, propylene, isopropylene, isopropylidene or one of thefollowing groups referred to as Z:

—O—; —CO—; —COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂—; —NR₇—CO—; in saidformulae, R₇ represents a hydrogen atom, a linear or branched alkylgroup having from 1 to 6 carbon atoms,

R₀ has the meaning given previously,

m is an integer from 0 to 4.

As specific examples, there can be mentioned2-(3-benzoylphenyl)propionic acid (Ketoprofen®),2-(4-isobutylphenyl)propionic acid (Ibuprofen®),2-(5-methoxynaphthyl)propionic acid (Naproxen®).

Selective asymmetrical hydrogenation of said substrates is carried outusing as catalysts the metallic complexes of the invention liganded byoptically active diphosphines of general formula (Ia) or (Ib).

When the diphosphine-transition metal complexes of the invention areused as asymmetrical hydrogenation catalysts of unsaturated carboxylicacids, the desired product can be obtained with a high optical yield.

By choosing one of the diphosphine optical isomers having a (+) or (−)rotatory power, and using a diphosphine-transition metal complexcomprising the chosen isomer, the unsaturated carboxylic acid ishydrogenated into a compound having the desired absolute configuration,with a high optical yield.

Hydrogenation is generally carried out at a temperature comprisedbetween 20 and 100° C.

The hydrogen pressure can be comprised between 0.1 and 200 bar, and morepreferentially between 1 and 150 bar.

The diphosphine/transition metal complex is used in such a manner thatthe ratio between the number of atoms of metal present in the complexand the number of moles of the compound to be hydrogenated is comprisedbetween 0.1 and 0.0001.

The hydrogenation process is preferably implemented in an organicsolvent. Any type of solvent is used provided it is stable under thereaction conditions.

A polar organic solvent is preferably used, and more particularly thefollowing solvents:

aliphatic, cycloaliphatic or aromatic ether-oxides, and moreparticularly diethylether, dipropylether, diisopropylether,dibutylether, methyltertiobutylether, ditertiobutylether, ethyleneglycoldimethylether, diethyleneglycol dimethylether; diphenylether,dibenzylether, anisole, phenetole, 1,4-dimethoxybenzene, veratrole,1,4-dioxane, tetrahydrofuran (THF),

mono- or polyhydroxylated alcohols and more particularly aliphaticmonoalcohols such as methanol, ethanol, propanol, butanol, sec-butanol,tert-butanol, pentanol, hexanol, aliphatic dialcohols such as ethyleneglycol, diethylene glycol, propylene glycol, cycloaliphatic alcoholssuch as cyclopentanol, cyclohexanol,

aliphatic ketones such as acetone, methylethylketone, diethylketone,

aliphatic esters such as in particular methyl acetate, ethyl acetate,propyl acetate.

The concentration of the substrate in the organic solvent advantageouslyvaries between 0.01 and 1 mol/l.

After the formation of the hydrogenation complex, a basic compound canoptionally be added.

This basic compound can be an alkaline base such as sodium or potassiumhydroxide or a primary, secondary or tertiary amine, and moreparticularly pyridine, piperidine, triethylamine and preferablytriethylamine.

The quantity of base added is such that the ratio between the number ofmoles of base and the number of metallic atoms present in thediphosphine/transition metal complex is comprised between 0 and 25,preferably between 0 and 12.

There follows a preferential implementation of the process of theinvention.

Said process is implemented in an autoclave which is purged using aninert gas, preferably nitrogen. The substrate is preferably loaded inthe organic solvent, then the catalyst also in solution in the organicsolvent.

The nitrogen is replaced with hydrogen.

Hydrogenation is completed when the hydrogen pressure becomes stable.

The hydrogenation process according to the invention provides access tothe different enantiomers of numerous derivatives.

As mentioned previously, the implementation of new dipshophinesaccording to the invention allows an improvement in the enantiomericexcess in certain asymmetrical catalysis reactions, in particular inallylic substitution reactions [M. YAMAGUSI et al., Tetrahedron Letters,31, p. 5049 (1990) and [M. MAYASHI et al., Tetrahedron Letters 27, p.191 (1986)].

As more specific examples illustrating this type of reaction, there canmore particularly be mentioned the reaction of esters, preferably1,3-diphenyl-3-acetoxypropene with alkyl esters of malonic acid,preferably dimethyl or diethyl malonate.

The reaction is carried out in the presence of a complex comprising anoptically active diphosphine and palladium: the ligand corresponding toone of the following formulae (Ia) or (Ib).

The palladium precursor preferentially chosen corresponds to the formula[Pd(allyl)Cl]₂.

The reaction is preferably carried out in a polar aprotic solvent, inparticular an aliphatic or aromatic halogenated hydrocarbon or in asolvent of nitrile type, preferably acetonitrile, an aliphatic,cycloaliphatic or aromatic ether oxide, and more particularly diethyloxide, dipropyl oxide, diisopropyl oxide, dibutyl oxide,methyltertiobutylether, dipentyl oxide, diisopentyl oxide,ethyleneglycol dimethylether (or 1,2-dimethoxyethane), diethyleneglycoldimethylether (or 1,5-dimethoxy 3-oxapentane); benzyl oxide; dioxane,tetrahydrofuran (THF).

Among said solvents, tetrahydrofuran is preferentially used.

The quantity of organic solvent used can vary very widely. The ratiobetween the number of moles of solvent and the number of moles ofsubstrate can thus range from 10 to 40 and is preferably comprisedbetween 20 and 25.

The molar ratio of the malonic acid ester/unsaturated substrategenerally varies between 1 and 5, preferably between 1 and 3.

The malonic acid ester which is reacted can be in the form of an anion.For this purpose, before reaction with the substrate, it is reacted witha nucleophile, preferably sodium hydride.

The hydride is used in a quantity ranging from the stoichiometricquantity to an excess, for example of 20%.

The reaction is advantageously carried out at low temperature,preferably between −10° C. and 10° C., preferably in the region of 0° C.

From a practical point of view, the malonic ester anion is first formedby reacting the malonic ester with sodium hydride, followed by addingthe substrate and the catalyst previously obtained by reacting thepalladium salt and the ligand, in an organic solvent, preferablytetrahydrofuran.

The reaction is advantageously carried out at ambient temperature, i.e.at a temperature generally ranging from 15° C. to 25° C.

The coupling product is obtained in allylic position.

The following examples illustrate the invention without however limitingit.

In Examples 1 to 4, new diphosphines are prepared.

Examples 5, 7 and 8 relate to the preparation of catalysts which areimplemented in application Examples 6, 9 and 10.

EXAMPLE 1

In this example, a diphosphine corresponding to the following formula isprepared:

Phospholyllithium

11.3 g (0.6 mol) of 1-phenyl-3,4-dimethylphosphole, 0.8 g of lithiummetal and 10 ml of distilled tetrahydrofuran are introduced into a 250ml flask.

The mixture is agitated under argon for 2 hours, in a cold water bath.

The solution becomes brown.

The appearance of phospholyllithium is checked by NMR ³¹P.

NMR ³¹P: δ(THF)=55.8 ppm .

In order to trap the phenyllithium, 2.7 g of aluminium chloride is addedat 0° C.

The medium is left to react for 30 minutes at 0° C.

1,1′-bis-(3,4-dimethylphosphole) (IV)

6 g (0.025 mol) of iodine in solution in 25 ml of tetrahydrofuran isadded dropwise at ambient temperature to the preceding mixture.

When 90% of this solution is introduced, the disappearance of (III) isverified by NMR ³¹P.

NMR ³¹P: δ(THF)=−22.4 ppm.

The 1,1′-bis-(3,4-dimethylphosphole) is extracted from the mixture usinghexane.

6,6′bis-(1-phospha-3 phenyl-2,4,5-trimethylnorbornadiene) in meso form(Im) and in racemic form (Ir)

The previous solution is evaporated to dryness, sheltered from the airand taken to 140° C.

Then 5.2 g of methylphenylacetylene is introduced and the medium is leftto react for 15 to 20 minutes.

The disappearance of 1,1′-bis-(3,4-dimethylphosphole) is again monitoredby NMR ³¹P.

The spectrum is composed of 2 singlets corresponding to twodiastereoisomers.

NMR ³¹P: δ(CH₂Cl₂)=−13.2 ppm (Im)

NMR ³¹P: δ(CH₂Cl₂)=−13.5 ppm (Ir)

The product is extracted with ether and washed with water.

The organic phases are combined then evaporated to dryness.

The residue is then purified by chromatography on a silica column(elution with hexane in order to eliminate the excessmethylphenylacetylene then with a mixture of hexane/dichloromethane:80/20 by volume).

The overall yield is 30%.

6,6′bis-(1-phospha-3-phenyl-2,4,5-trimethylnorbornadiene) dioxide inmeso form (IXm) and in racemic form (IXr)

The (Im)+(Ir) mixture obtained previously is dissolved in 50 ml oftoluene and oxidized with 10 ml of a hydrogen peroxide solution at 30%by weight of hydrogen peroxide introduced in excess. The mixture is thenheated at 70° C. for 2 hours under mechanical agitation.

The disappearance of (Im)+(Ir) is again monitored by NMR ³¹P.

After cooling down the aqueous phase is decanted. The organic solutionis washed once with sodium thiosulphate (10 ml of saturated solution)and once with water (10 ml).

After drying over sodium sulphate and evaporation of the solvent, an oilis recovered the NMR ³¹P spectrum of which is constituted by a mixtureof two diastereoisomers (IXm) and (IXr).

NMR ³¹P: δ(CH₂Cl₂)=50.2 ppm (IXm)

NMR ³¹P: δ(CH₂Cl₂)=53.1 ppm (IXr)

The two diastereoisomers are separated by chromatography on a silicacolumn with elution with ethyl acetate then a mixture of ethylacetate/methanol (90/10 by volume).

The overall yield of (IXm)+(IXr) is 90%.

Reduction of (IXr) to Diphosphine (Ir)

1.55 g (0.003 mol) of racemic (IXr) and 10 ml of toluene are introducedinto a 100 ml flask.

1.42 of distilled pyridine is added at ambient temperature, then 0.81 gof trichlorosilane is added dropwise and the mixture is heated for 10minutes at 80° C. The reaction is monitored by NMR ³¹P.

The excess trichlorosilane is neutralized with an aqueous solution ofsoda at 30% by weight, then the aqueous phase is extracted three timeswith ether, the organic phases are combined then washed with a saturatedsolution of sodium chloride.

The organic phase is dried over magnesium sulphate and evaporated underreduced pressure.

The phosphine (Ir) thus obtained is purified on a column of deactivatedsilica gel (elution dichloromethane).

The overall yield of the reduction is 95%.

The characterization of the racemic mixture (Ir) is as follows:

NMR ³¹P: δ(toluene)=−13.5 ppm

NMR ¹H: δ(CDCl₃)=1.02 (s, 6H, CH₃); 1.4-2.1 (m, 16H, CH₂ bridge, CH₃);6.8-7.4 (m, 20 H, phenyl).

Binuclear Complex of Palladium II (XIIa) and (XIIb).

243 mg (0.5 mmol) of racemic (Ir) and 300 mg (0.05 mmol) of(−)-di-μ-chloro-bis[(S)-N,N-dimethyl-α-phenylethylamine-2C,N)]dipalladiumII are introduced into 12 ml of toluene.

Complexing is rapid and is followed by NMR ³¹P.

The brown solution is evaporated to dryness and the residue ischromatographed in order to separate the two diastereoisomers (elutiontoluene/ethyl acetate: 90/10 by volume).

In this way the two pure isolated enantiomers are recovered in the formof two diastereoisomer complexes of formula (XIIa) and (XIIb).

NMR ³¹P: δ(toluene)=54.3 ppm (XIIa)

NMR ³¹P: δ(toluene)=47.8 ppm and 43.2 ppm (XIIb)

Decomplexing of (XIIa) or (XIIIb)

270 mg of (XIIa) (0.25 mmol) and 10 ml of dichloromethane are introducedinto a 100 ml flask.

Then 0.5 g of sodium cyanide and a few milliliters of water (3 ml) areadded.

Vigorous agitation is carried out under argon for 10 to 15 minutes.

The diphosphine (Ia) is then extracted with dichloromethane.

The organic phase is washed with water then dried over sodium sulphate.

In this way pure (Ia) of formula

is recovered.

The overall yield for the separation of diastereoisomers is 90%.

NMR ³¹P: δ(CDCl₃)=−13.5 ppm [α]_(D)=+57° (c=1, CH₂Cl₂) (Ia)

NMR ³¹P: δ(CDCl₃)=−13.5 ppm [α]_(D)=+55° (c=1, CH₂Cl₂) (Ib)

EXAMPLE 2

In this example, a diphosphine is prepared corresponding to thefollowing formula:

Phospholyllithium

It is prepared according to the operating method of Example 1.

1,1′-bis-(3,4-dimethylphosphole) (IV)

It is synthesized as in Example 1.

6,6′bis-(1-phospha-3 phenyl-4,5-dimethylnorbomadiene) in meso form (Im)and in racemic form (Ir)

The previous solution is evaporated to dryness, sheltered from the airand taken to 140° C.

Then 4.6 g of phenylacetylene is introduced and the medium is left toreact for 15 to 20 minutes.

The disappearance of 1,1′-bis-(3,4-dimethylphosphole) is again monitoredby NMR ³¹P.

The spectrum is composed of 2 singlets corresponding to twodiastereoisomers.

NMR ³¹P: δ(toluene)=−30.0 ppm (Ir)

NMR ³¹P: δ(toluene)=−29.5 ppm (Im)

The product is extracted with ether and washed with water.

The organic phases are combined then evaporated to dryness.

The residue is then purified by chromatography on a silica column(elution with hexane in order to eliminate the excess phenylacetylenethen with a mixture of hexane/dichloromethane: 80/20 by volume).

The overall yield is 25%.

6,6′bis-(1-phospha-3-phenyl-4,5-dimethylnorbornadiene) dioxide in mesoform (IXm) and in racemic form (IXr)

The Im+Ir mixture obtained previously is dissolved in 50 ml of tolueneand oxidized with 10 ml of a hydrogen peroxide solution at 30% by weightof hydrogen peroxide introduced in excess. The mixture is then heated at70° C. for 30 minutes under mechanical agitation.

The disappearance of (Im)+(Ir) is again monitored by NMR ³¹P.

After cooling down the aqueous phase is decanted. The organic solutionis washed once with a saturated solution of sodium thiosulphate (10 ml)and once with water (10 ml).

After drying over sodium sulphate and evaporation of the solvent, an oilis recovered the NMR ³¹ P spectrum of which is constituted by a mixtureof two diastereoisomers (IXm) and (IXr).

NMR ³¹P: δ(toluene)=47.3 ppm (IXr)

NMR ³¹P: δ(toluene)=45.8 ppm (IXm)

The two diastereoisomers are separated by chromatography on a silicacolumn with elution with ethyl acetate then a mixture of ethylacetate/methanol (90/10 by volume).

The overall yield of (IXm)+(IXr) is 90%.

Reduction of (IXr) to Diphosphine (Ir)

1.46 g (0.003 mol) of racemic (IXr) and 10 ml of toluene are introducedinto a 100 ml flask.

2.4 of distilled pyridine is added at ambient temperature, then 1.1 g oftrichlorosilane is added dropwise and the mixture is heated for 10minutes at 80° C. The reaction is monitored by NMR ³¹P.

The excess trichlorosilane is neutralized with an aqueous solution ofsoda at 30% by weight, then the aqueous phase is extracted three timeswith ether, the organic phases are combined then washed with a saturatedsolution of sodium chloride.

The organic phase is dried over magnesium sulphate and evaporated underreduced pressure.

The phosphine (Ir) thus obtained is purified on a column of deactivatedsilica gel (elution dichloromethane).

The overall yield of the reduction is 95%.

The characterization of the racemic mixture (Ir) is as follows:

NMR ³¹P: δ(toluene)=−30.0 ppm

NMR ¹H: δ(CDCl₃)=1.42 (s, 6H, CH₃); 1.82 (s, 6H, CH₃); 2.04-2.11(m, 4H,CH₃); 6.85 (d, 2H, ²J(H-P)=44 Hz); 7.1-7.4 (m, 10H, Ph).).

Binuclear Complex of Palladium II (XIIa) and (XIIIb)

215 mg (0.5 mmol) of racemic (Ir) and 300 mg (0.05 mmol) of(+)-di-μ-chloro-bis[(S)-N,N-dimethyl-α-phenylethylamine-2C,N)]dipalladiumII are introduced into 12 ml of toluene under nitrogen.

Complexing is rapid and is followed by NMR ³¹P.

The brown solution is evaporated to dryness and the residue ischromatographed in order to separate the two diastereoisomers (elutiontoluene/ethyl acetate: 90/10 by volume).

In this way the two pure isolated enantiomers are recovered in the formof two diastereoisomer complexes of formula (XIIa) and (XIIIb).

NMR ³¹P: δ(toluene)=37.4 ppm [α]_(D)=−77° (c=1, CH₂Cl₂) (XIIa)

NMR ³¹P: δ(toluene)=33.1 ppm and 25.2 ppm [α]_(D)89° (c=1, Cl₂Cl₂)(XIIIb)

Decomplexing of (XIIa) or (XIIIb)

250 mg of (XIIa) (0.25 mmol) and 10 ml of dichloromethane are introducedinto a 100 ml flask.

Then 0.5 g of sodium cyanide and a few milliliters of water (3 ml) areadded.

Vigorous agitation is carried out under argon for 10 to 15 minutes.

The diphosphine (Ia) is then extracted with dichloromethane.

The organic phase is washed with water then dried over sodium sulphate.

In this way pure (Ia) of formula

is recovered.

The overall yield of the decomplexing is 90%.

NMR ³¹P: δ(CDCl₃)=−30.0 ppm [α]_(D)=+205.7° (c=1, CH₂Cl₂) (Ia)

NMR ³¹P: δ(CDCl₃)=−30.0 ppm [α]_(D)=−200.2° (c=1, CH₂Cl₂) (Ib)

EXAMPLE 3

In this example, a diphosphine is prepared corresponding to thefollowing formula:

Phospholyllithium

It is prepared according to the operating method of Example 1.

1,1′-bis-(3,4-dimethylphosphole) (IV)

It is synthesized as in Example 1.

6,6′bis-(1-phospha-2-tert-butyl-3-phenyl-4,5-dimethylnorbomadiene) inmeso form (Im) and in racemic form (Ir)

10 g of tert-butylacetylene is reacted with 7 g of1,1′-bis-(3,4-dimethylphosphole) and the medium is left to react for 15minutes at 140° C.

6,6′bis-(1-phospha-2-tert-butyl-3-phenyl-4,5-dimethylnorbomadiene)dioxide in meso form (IXm) and in racemic form (IXr)

The (Im)+(Ir) mixture obtained previously is dissolved in 50 ml oftoluene and oxidized with 4.5 g of a hydrogen peroxide solution at 30%by weight of hydrogen peroxide introduced in excess. The mixture is thenheated at 70° C. for 3 hours under mechanical agitation.

The disappearance of (Im)+(Ir) is again monitored by NMR ³¹P. Aftercooling down the aqueous phase is decanted. The organic solution iswashed once with sodium thiosulphate (10 ml of saturated solution) andonce with water (10 ml).

After drying over sodium sulphate and evaporation of the solvent, an oilis recovered (overall yield=26%) the NMR ³¹P spectrum of which isconstituted by a mixture of two diastereoisomers (IXm) and (IXr).

NMR ³¹P: δ(CH₂Cl₂)=49.7 ppm (IXr)

NMR ³¹P: δ(CH₂Cl₂)=49.9 ppm (IXm)

The two diastereoisomers are separated by chromatography on a silicacolumn with elution with ethyl acetate then a mixture of ethylacetate/methanol (95/05 by volume).

The overall yield of (IXm)+(IXr) is 100%.

Reduction of (IXr) to Diphosphine (Ir)

The reduction of 1.2 g of diphosphine dioxide (IXr) is carried out.

The phosphine (Ir) thus obtained is purified on a column of deactivatedsilica gel (elution dichloromethane).

The overall yield of the reduction is 89%.

Binuclear Complex of Palladium II (XIIa) and (XIIIb)

1.24 g (1.87 mmol) of racemic (Ir) and 1 g (1.87 mmol) of(−)-di-μ-chloro-bis[(S)-N,N-dimethyl-α-phenylethylamine-2C,N)]dipalladiumII are introduced into 12 ml of toluene.

1.87 g of palladium complexes are obtained.

The diastereoisomers are separated by chromatography on silica gel witha toluene/ethyl acetate mixture 90/10).

0.85 g of complex (XIIa) (yield=45%) and 0.8 g of complex (XIIIb)(yield=44%) are recovered with the following NMR characteristics:

NMR ³¹P: δ(CH₂Cl₂)=36.7 ppm [α]_(D)=−61.7° (c=9.3, CH₂Cl₂) (XIIa)

NMR ³¹P: δ(CH₂Cl₂)=36.72 ppm [α]_(D)=317.1° (c=10.6, CH₂Cl₂) (XIIIb)

Decomplexing of (XIIa) or (XIIb).

A decomplexing is carried out with sodium cyanide, in dichloromethane,as described previously.

The diphosphine (Ia) is then extracted with dichloromethane.

The organic phase is washed with water then dried over sodium sulphate.

In this way the compound of formula

is recovered.

The overall yield of the decomplexing is 85%.

NMR ³¹P: δ(toluene)=−17.3 ppm [α]_(D)=+6° (c=1, CH₂Cl₂)

NMR ³¹P: δ(toluene)=−17.3 ppm [α]_(D)=−6° (c=1, CH₂Cl₂)

EXAMPLE 4

In this example a diphosphine is prepared corresponding to the followingformula:

Phospholyllithium

It is prepared according to the operating method of Example 1.

1,1′-bis-(3,4-dimethylphosphole) (IV)

It is synthesized as in Example 1.

6,6′bis-(1-phospha-2-phenyl-3-mesityl-4,5-dimethylnorbornadiene) in mesoform (Im) and in racemic form (Ir)

14 g of mesitylphenylacetylene (63.3 mmol) is reacted with 7 g of1,1′-bis-(3,4-dimethylphosphole) (31.65 mol) and the medium is left toreact for 15 minutes at 140° C.

6,6′bis-(1-phospha-2-phenyl-3-mesityl-4,5-dimethylnorbomadiene) dioxidein meso form (IXm) and in racemic form (IXr)

The (Im)+(Ir) mixture obtained previously is dissolved in 50 ml oftoluene and oxidized with 4.6 g of a hydrogen peroxide solution at 30%by weight of hydrogen peroxide introduced in excess. The mixture is thenheated at 70° C. for 3 hours under mechanical agitation.

The disappearance of (Im)+(Ir) is again monitored by NMR ³¹P. Aftercooling down the aqueous phase is decanted. The organic solution iswashed once with sodium thiosulphate (10 ml of saturated solution) andonce with water (10 ml).

After drying over sodium sulphate and evaporation of the solvent, 4.6 gof an oil is recovered (overall yield=21%) the NMR ³¹P spectrum of whichis constituted by a mixture of two diastereoisomers (IXm) and (IXr).

NMR ³¹P: δ(toluene)=47.4 ppm (IXr)

NMR ³¹P: δ(toluene)=48.4 ppm (IXm)

The two diastereoisomers are separated by chromatography on a silicacolumn with elution with ethyl acetate then a mixture of ethylacetate/methanol (95/05 by volume).

The overall yield of (IXm)+(IXr) is 100%.

Reduction of (IXr) to diphosphine (Ir)

The reduction of 1.2 g of diphosphine dioxide (IXr) is carried out.

The phosphine (Ir) thus obtained is purified on a column of deactivatedsilica gel (elution dichloromethane).

The overall yield of the reduction is 90%.

Binuclear Complex of Palladium II (XIIa) and (XIIb).

1.2 g (1.7 mmol) of racemic (Ir) and 0.8 g (1.7 mmol) of(−)-di-μ-chloro-bis[(S)-N,N-dimethyl-α-phenylethylamine-2C,N)]dipalladiumII are introduced into 12 ml of toluene.

1.74 g of palladium complexes are obtained.

The diastereoisomers are separated by chromatography on silica gel witha toluene/ethyl acetate mixture (90/10).

The following are recovered:

0.8 g (yield=45%) of an optically active complex (XIIa) having thefollowing characteristics:

NMR ³¹P: δ(CH₂Cl₂)=59.2 ppm [α]_(D)=+300° (c=11.1, CH₂Cl₂)

and 0.75 g (yield=44%) of an optically active complex (XIIIb) having thefollowing characteristics:

NMR ³¹P: δ(CH₂Cl₂)=58.1 ppm [α]_(D)=−280° (c=10, CH₂Cl₂)

Decomplexing of (XIIa) or (XIIIb)

A decomplexing is carried out with sodium cyanide, in dichloromethane,as described previously.

The diphosphine is then extracted with dichloromethane.

The organic phase is washed with water then dried over sodium sulphate.

In this way the compound of formula

is recovered.

The overall yield of the decomplexing is 85%.

NMR ³¹P: δ(toluene)=−9.5 ppm [α]_(D)=+114° (c=9.5, CH₂Cl₂)

NMR ³¹P: δ(toluene)=−9.5 ppm [α]_(D)32 −114° (c=9.5, CH₂Cl₂)

EXAMPLE 5

In this example, the preparation of a complex of formula[Rh⁺(COD)(P*P)]PF₆ ⁻ is described in which COD represents1,5-cyclooctadiene and (P*P) represents the diphosphine of formula (Ia)of Example 1.

11.6 mg of Rh(COD)₂PF₆ is dissolved under argon in 3 ml of acetone in a10 ml schlenk tube.

A solution of 11.3 mg of said diphosphine in acetone is then addeddropwise, still under an inert gas atmosphere.

After agitation for a few minutes, the expected complex is obtained.

NMR ³¹P: δ=−61.6 ppm, J(Rh-P)=155 Hz.

EXAMPLE 6

In this example, the asymmetrical hydrogenation of the followingcompound is carried out, using the catalyst of Example 5:

400 mg of said compound is dissolved in a flask in 20 ml of methanol.

Then, the metallic complex as proposed in Example 5 is prepared.

The acetone is evaporated off and the residue is dissolved in 5 ml ofmethanol.

Then, the two solutions are introduced into an autoclave which has beenpurged beforehand and maintained under a nitrogen atmosphere.

Then, hydrogen is introduced up to a pressure of 3 atmospheres.

Agitation is carried out for 1 hour at 20° C.

The excess hydrogen is removed and the reaction solution is recovered.

The solvent is evaporated off and the residue analyzed by NMR¹H in orderto verify the progress of the reaction.

The reaction is quantitative.

The enantiomeric excess is determined by chiral high performance liquidchromatography (chiral protein HSA column 150×6.4 mm Shandon®) and theabsolute configuration of the product by measurement of the α_(D) bypolarimetry.

With the diphosphine of Example 1, ee=35%, [α_(D)] (ethanol, c=1)<0.

EXAMPLE 7

In this example, the preparation of a catalyst is described which isobtained by the reaction of a palladium complex [PdCl(allyl)]₂ and thediphosphine of Example 3 having an [α_(D)]=+6° (c=1, CH₂Cl₂).

1.83 mg (0.005 mmol) of palladium complex [PdCl(allyl)]₂ is solubilizedin 0.2 ml of tetrahydrofuran, 0.01 mmol of said diphosphine in 0.3 ml oftetrahydrofuran is added and the mixture is left for 15 minutes, underagitation, at ambient temperature.

EXAMPLE 8

In this example, the preparation of a catalyst is described which isobtained by the reaction of a palladium complex [PdCl(allyl)]₂ and thediphosphine of Example 4: the diphosphine used having an [α_(D)]=+114°(c=9.5, CH₂Cl₂).

1.83 mg (0.005 mmol) of palladium complex [PdCl(allyl)]₂ is solubilizedin 0.9 ml of tetrahydrofuran, 0.01 mmol of said diphosphine in 0.3 ml oftetrahydrofuran is added and the mixture is left for 15 minutes, underagitation, at ambient temperature.

EXAMPLES 9 AND 10

In these examples, an allylic substitution reaction is carried out.

72 mg of sodium hydride (1.8 mmol) in 2 ml of hexane is placed in aschlenk tube under argon and the mixture is agitated for 1 minute thenthe hexane is removed.

4 ml of tetrahydrofuran is added to the sodium hydride followed by 0.23ml of ethyl malonate (2 mmol) at 0° C.

An anion forms and the medium is taken to ambient temperature then 250mg of 1,3-diphenylpropenyl acetate (1 mmol) prepared according toBosnich et al. [J. Am. Chem. Soc. 107, 2033 (1985)] in solution in 1 mlof tetrahydrofuran and then the catalytic system are added.

The medium is heated to the reflux temperature of the solvent.

After total reaction, the reaction medium is hydrolyzed with 4 ml ofacetic acid then extracted with ether.

The organic phase is washed with water, dried over anhydrous magnesiumsulphate then evaporated under reduced pressure of 25 mm of mercury.

The residue is chromatographed on silica gel, with the followingeluants: hexane/ethyl acetate 80/20 for the starting allyl Rf=0.4 andRf=0.3 for the product formed.

The two catalysts of Examples 7 and 8 allow 1,3-diphenylpropenyldimethylmalonate to be obtained, after heating for one hour with a yieldand an enantiomeric excess (ee) stated in the following Table 1:

TABLE 1 Ex. No. Nature of catalyst Yield (%) Enantiomeric excess (%)  9Example 7 90 55 10 Example 8 94 45

EXAMPLE 11

The diphosphine of Example 1 is prepared according to the same operatingmethod except for the fact that the meso and d/l diastereoisomers areseparated according to a sulphide then oxide route.

6,6′bis-(1-phospha-3-phenyl-2,4,5-dimethylnorbomadiene) disulphide inracemic form (IX′r)

The operation starts with the preparation of6,6′bis-(1-phospha-3-phenyl-2,4,5-dimethylnorbornadiene) in meso form(Im) and in racemic form (Ir) according to the same operating method asExample 1.

4.9 g of this mixture are solubilized in 20 ml of toluene then 1.65 g ofsulphur is added.

The mixture is heated for 20 minutes at 80° C.

5.3 g of diastereoisomers are obtained which are then separated onsilica gel with ethyl acetate as eluant.

The first diastereoisomer (1.75 g) corresponds to the racemic mixture(Rf=0.29 and yield=30%) and has the following NMR characteristics:

NMR ³¹P: δ(toluene)=51 ppm

The second diastereoisomer (3.5 g) corresponds to meso (Rf=0.17 andyield=70%) and has the following NMR characteristics:

NMR ³¹P: δ(ethyl acetate) δa=51.05 ppm and δb=53.75 ppm (AB, ³JPP=6.5Hz).

6,6′bis-(1-phospha-3-phenyl-2,4,5-dimethylnorbornadiene) dioxide inracemic form (IXr)

1.25 g (2.4 mmol) of the first diastereoisomer obtained previously issolubilized, under a current of argon, in 10 ml of CH₂Cl₂, then 1.1 g ofCF₃COOH (9.65 mmol) and 0.95 of cyclohexene oxide (9.65 mmol) are added.

The mixture is heated at reflux of the solvent for 30 minutes.

The excess acid is neutralized with a solution of sodium carbonate thenthe aqueous phase is extracted with ether.

The organic phases are combined and dried over anhydrous magnesiumsulphate.

The solvent is evaporated off.

The residue is purified by chromatography on silca gel with an ethylacetate/methanol mixture (90/10).

1.12 g of racemic diphosphine dioxide is obtained i.e. a yield of 95%.

The NMR characteristics of the racemic mixture are as follows:

NMR ³¹P: δ(CH₂Cl₂)=53.1 ppm (IXr)

Then the two enantiomers are separated after reduction of the racemicdiphosphine dioxide according to the same operating method of Example 1.

What is claimed is:
 1. A 6,6′-bis-(1-phosphanorbornadiene) diphosphinecorresponding to formula (I):

wherein: (a) R₁, R₂, R₃, R₄, and R₅ are the same or different and areselected from the group consisting of a hydrogen atom, an acyclicaliphatic radical, an aromatic radical, a carbocyclic radical, aheterocyclic radical, and an aliphatic radical having a cyclicsubstituent; wherein R₄ and R₅ cannot simultaneously represent anunsubstituted phenyl group; (b) R₁ and R₄ are as defined in (a) above,R₅ is as defined in (a) above or (c) below, and R₂ and R₃ together forma saturated or unsaturated ring; or (c) R₁, R₂, R₃ and R₄ are as definedin (a) and (b) above, and R₅ is

wherein R₁′, R₂′ and R₃′ have the same meaning as R₁, R₂ and R₃,respectively.
 2. The 6,6′-bis-(1-phosphanorbornadiene) diphosphineaccording to claim 1, wherein the acyclic aliphatic radical is ahydrocarbon radical having 1 to 40 carbon atoms.
 3. The6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim 1,wherein the acyclic aliphatic radical, the carbocyclic radical, theheterocyclic radical and the aliphatic radical carrying a cyclicsubstituent are saturated or unsaturated.
 4. The6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim 1,wherein the acyclic aliphatic radical and the aliphatic radical carryinga cyclic substituent are linear or branched.
 5. The6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim 1,wherein the carbocyclic radical, the heterocyclic radical, the aromaticradical and the aliphatic radical carrying a cyclic substituent aremonocyclic or polycyclic.
 6. An optically active6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim 1,having the formula (Ia):


7. An optically active 6,6′-bis-(1-phosphanorbornadiene) diphosphineaccording to claim 1, having the formula (Ib):


8. The 6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim1 in meso form having the formula (Im):


9. The 6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim1, comprising a racemic mixture of optically active compounds having theformulae:


10. The diphosphine according to claim 1, wherein R₁, R₂, R₃, R₄ and R₅are identical or different, and represent: (a) a linear or branched,saturated or unsaturated acyclic aliphatic radical, the hydrocarbonchain being optionally interrupted by a heteroatom and/or optionallycarrying substituents; (b) a linear or branched, saturated orunsaturated acyclic aliphatic radical having an optionally substitutedcyclic substituent; (c) a carbocylic radical which is saturated or whichcomprises 1 or 2 unsaturations in the ring, and wherein the ring isoptionally substituted; (d) a saturated or unsaturated polycycliccarbocylic radical, the number of carbon atoms in each ring varyingbetween 3 and 6, and wherein each ring is optionally substituted; (e) apolycyclic aromatic hydrocarbon radical, wherein the rings areoptionally substituted and wherein the rings optionally formortho-condensed or ortho- and peri-condensed systems; (f) a saturated,unsaturated or aromatic heterocyclic radical, wherein the carbon atomsof the heterocyclic ring are optionally substituted; (g) a polycyclicheterocyclic radical selected from the group consisting of a radicalconstituted by at least 2 aromatic or non-aromatic heterocyclescontaining at least one heteroatom in each ring and together formingortho- or ortho- and peri-condensed systems, and a radical constitutedby at least one aromatic or non-aromatic hydrocarbon ring and at leastone aromatic or non-aromatic heterocycle together forming ortho- orortho- and peri-condensed systems; wherein the carbon atoms of saidrings are optionally substituted.
 11. The diphosphine according to claim10, wherein the saturated, unsaturated or aromatic heterocyclic radicalcomprises 5 or 6 total atoms in the ring and wherein 1 or 2 of the atomsin the ring are heteroatoms.
 12. The diphosphine according to claim 1,wherein R₁, R₂, R₃, R₄ and R₅ are identical or different, and representan aromatic hydrocarbon radical or a benzene radical corresponding togeneral formula (II):

wherein: (a) n is an integer from 0 to 5, (b) Q represents R₀ or R₀′,wherein R₀ represents: (i) a linear or branched alkyl radical havingfrom 1 to 6 carbon atoms; (ii) a linear or branched alkenyl radicalhaving from 2 to 6 carbon atoms; (iii) a linear or branched alkoxyradical having from 1 to 6 carbon atoms; (iv) an acyl group having from2 to 6 carbon atoms; or (v) a radical selected from the group consistingof —R₆—OH, —R₆—COOR₇, —R₆—CHO, —R₆—NO₂, —R₆—CN, —R₆—N(R₇)₂,—R₆—CO—N(R₇)₂, —R₆—SH, —R₆—X, —R₆—CF₃, and —O—CF₃, wherein R₆ representsa valency bond or a saturated or unsaturated, linear or branched,divalent hydrocarbon radical having from 1 to 6 carbon atoms; R₇represents a hydrogen atom or a linear or branched alkyl radical havingfrom 1 to 6 carbon atoms; and X represents a halogen atom, and whereinR₀′ represents:

 in which: m is an integer from 0 and 5; R₀ has the meaning indicatedpreviously; and R₈ represents a valency bond; a saturated orunsaturated, linear or branched divalent hydrocarbon group having from 1to 6 carbon atoms; —O—; —CO—; COO—; —NR₇—; —CO—NR₇—; —S—; —SO₂—; or—NR₇—CO—; wherein R₇ represents a hydrogen atom or a linear or branchedalkyl group having from 1 to 6 carbon atoms.
 13. The diphosphineaccording to claim 1, wherein the R₂ and R₃ radicals together form asaturated or unsaturated ring.
 14. The diphosphine according to claim13, wherein the R₂ and R₃ radicals together form a saturated orunsaturated ring having from 5 to 7 carbon atoms.
 15. The diphosphineaccording to claim 1, wherein: (a) R₁ and R₂ are a hydrogen atom or alinear or branched alkyl radical having from 1 to 4 carbon atoms; (b) R₃is a radical other than a hydrogen atom; and (c) R₄ and R₅ are ahydrogen atom, an alkyl radical, or a phenyl radical.
 16. The6,6′-bis-(1-phosphanorbornadiene) diphosphine according to claim 1,wherein: (a) R₂ and R₃ form together a saturated or unsaturated ring;and (b) R₅ is sterically hindered.
 17. The diphospine according to claim16, wherein R₅ is: (a) a branched aliphatic radical having a tertiaryradical located in the b position with respect to the phosphorus atom;(b) a phenyl radical carrying at least one substituent; or (c) anaphthyl radical.
 18. The diphosphine according to claim 16, wherein theR₁, R₂, R₃ and R₄ radicals are identical or different, and represent:(a) an acyclic aliphatic radical, the hydrocarbon chain being optionallyinterrupted by a heteroatom and/or optionally carrying substituents; (b)an acyclic aliphatic radical having an optionally substituted cyclicsubstituent; (c) a carbocyclic radical which is saturated or comprises 1or 2 unsaturations in the ring; (d) a saturated or unsaturatedpolycyclic carbocyclic radical, the number of carbon atoms in each ringvarying between 3 and 6; (e) a polycyclic aromatic hydrocarbon radical;(f) a heterocyclic radical comprising 5 or 6 atoms in the rings and 1 or2 heteroatoms; or (g) a polycyclic heterocyclic radical selected fromthe group consisting of: a radical constituted by at least 2 aromatic ornon-aromatic heterocycles containing at least one heteroatom in eachring and together forming ortho- or ortho- and peri-condensed systems;and a radical constituted by at least one aromatic or non-aromatichydrocarbon ring and at least one aromatic or non-aromatic heterocycletogether forming ortho- or ortho- and peri-condensed systems.
 19. Thediphosphine according to claim 1, which corresponds to one of theformulae:


20. A method for the preparation of the diphosphine of claim 1,comprising: (a) rearranging a diphosphole of formula IV

into a diphosphole of formula III

(b) reacting the diphosphole of formula III with an acetylenic compoundof formula (V):

to form the diphosphine of formula (I), wherein R₁, R₂, R₃, R₄ and R₅ informulae III-V are defined the same as in formula I.
 21. The method ofclaim 20, wherein the diphosphole of formula (III) is obtained from adiphosphole of formula (IV) by thermal treatment carried out at atemperature between 100° C. and 200° C.
 22. The method of claim 20,wherein the diphosphole of formula (IV) is1,1′-bis-(3,4-dimethylphosphole), 1,1′-bis-(3-methylphosphole), or1,1′-bis-(phosphole).
 23. The method of claim 20, wherein the acetyleniccompound of formula (V) is selected from the group consisting ofacetylene, methyl acetylene, tert-butyl acetylene, phenyl acetylene,phenyl-methyl acetylene, o-tolyl acetylene, bis-(o-tolyl acetylene),phenyl-tert-butyl-acetylene, phenyl-mesityl acetylene andbis-(mesityl)acetylene.